Identification of Prolactin-Like Proteins Synthesized by Normal Murine Lymphocytes

Montgomery, David W.; LeFevre, Jane A.; Ulrich, Ellen D.; Adamson, Cynthia; Zukoski, Charles F.

doi:10.1210/endo-127-5-2601

Cited by 78 publications

(19 citation statements)

References 4 publications

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“…The Burkitt lymphoma cell line AG-876 also synthesized a 60-kDa form of prolactin and contained human prolactin mRNA detectable by PCR. These data are consistent with studies that demonstrated a prolactin-like protein in a B-lymphoma cell line (5) and mouse splenocyte lysates (13,14), with a molecular mass of 48 kDa or 22 kDa.…”

Section: Discussionsupporting

confidence: 92%

Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation.

Sabharwal

Glaser

Lafuse

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

195

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Prolactin has been shown to have an immunoregulatory role in the rodent immune response. A prolactinlike molecule has also been found in mouse splenocytes and a human B-lymphoblastoid cell line. We have evaluated whether human peripheral blood mononuclear cells (PBMCs) synthesize and/or secrete prolactin. We used the polymerase chain reaction (PCR) to generate a 276-base-pair prolactin product from human PBMCs, and Southern blot analysis confirmed that it was related to prolactin. Western blotting using a polyclonal antibody to prolactin indicated that cell extracts prepared from human PBMCs contained a high molecular mass (60-kDa) immunoreactive prolactin. To determine whether this PBMC prolactin was being secreted, we developed a highly sensitive and specific hormonal enzyme-linked immunoplaque assay. With this assay, we were able to detect human prolactin secretion from concanavalin A (Con A)-or phytohemagglutinin-stimulated PBMCs but not from unstimulated PBMCs. We next sought to determine whether this secreted prolactin could function as an autocrine growth factor in lymphoproliferation. We observed that anti-human prolactin antiserum significanly inhibited human PBMC proliferation in response to Con A or phytohemagglutinin. We conclude that a prolactin-like molecule is synthesized and secreted by human PBMCs and that it functions in an autocrine manner as a growth factor for lymphoproliferation.Recent studies suggest an immunoregulatory role for prolactin in rodents. In animals, hypophysectomy results in cessation of the growth of the thymus gland (1), decreased antibody titers against sheep red blood cells, and depressed delayed hypersensitivity reaction to chlorodinitrobenzene (2). Bromocryptine-induced hypoprolactinemia in mice injected with Listeria monocytogenes increases mortality that is associated with impaired lymphocyte proliferation and decreased production of macrophage-activating factors by T lymphocytes (3). Further, a prolactin-like molecule is secreted following Con A stimulation of murine lymphocytes (4), and a prolactin-like mRNA as well as a secreted product have been detected in human B-lymphoblastoid cell lines (5, 6). In contrast, Clevenger et al. (7) could not demonstrate prolactin-specific mRNA or prolactin secretion following interleukin 2 stimulation of a mouse T-lymphocyte line.Several investigators (7-9) using rodent lymphoid cell lines or splenocytes have found that a prolactin-like protein is required for lymphocyte mitogenesis. The relevance of these observations to human cellular immunity has not been explored. Here we document that human peripheral blood mononuclear cells (PBMCs) synthesize and secrete a prolactin-like molecule that functions in an autocrine loop as a growth factor for lymphoproliferation. MATERIALS AND METHODSOligonucleotide Primer Design. The sequences and positions of the two 21-mer primers used for PCR amplification of human prolactin cDNA are shown in Fig. 1 (10). The 5' primer is located within exon 3 of the human prolactin gene and the 3' pri...

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Section: Discussionsupporting

confidence: 92%

Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation.

Sabharwal

Glaser

Lafuse

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

195

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“…The expression of a functional HuGH-R on human neutrophils may therefore be subject to post-translational regulation. It is also important that both PRL- (33)(34)(35)(36) and GH-(37-39) like molecules are synthesized by lymphoid cells and that PRL augments a number ofimmune responses such as contact sensitivity reactions (4,40), synthesis of interferon-y (41) and expression of receptors for interleukin 2 (42).…”

Section: Discussionmentioning

confidence: 99%

Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor.

Fu¹,

Arkins²,

Fuh³

et al. 1992

J. Clin. Invest.

116

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Recombinant human growth hormone (HuGH) and human prolactin (HuPRL), but not GH of bovine or porcine origin, prime human neutrophils for enhanced superoxide anion (O°) secretion. Since HuGH, but not GH of other species, effectively binds to the HuPRL receptor (HuPRL-R), we used a group of HuGH variants created by site-directed mutagenesis to identify the receptor on human neutrophils responsible for HuGH priming. A monoclonal antibody (MAb) directed against the HuPRL-R completely abrogated O2 secretion by neutrophils

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“…The dramatic decrease in the DP CD4+8+ thymocyte population with anti-mPRL antiserum treatment suggests that a thymocyte-derived PRL or a related factor (14)(15)(16)(17) (Fig. 3a).…”

mentioning

confidence: 99%

“…Evidence supporting the role for PRL in these processes is largely derived from the use of animal models with reduced PRL, such as in hypopituitary dwarf mice, bromocryptine-or PRL-antiserum-treated mice, and aged rats (4)(5)(6)(7)(8)(9)(10)(11). Prolactin-deficient animals display immunological deficits such as underdeveloped thymuses associated with a reduction in double-positive (DP) CD4+8+ thymocytes and an accumulation of double-negative (DN) (12,13) and the identification of a lymphocyte-derived PRL (13)(14)(15)(16)(17) substantiates the involvement of PRL in the regulation of immune processes at several levels.…”

mentioning

confidence: 99%

Prolactin increases CD4/CD8 cell ratio in thymus-grafted congenitally athymic nude mice.

Gaufo

Diamond

1996

Proc. Natl. Acad. Sci. U.S.A.

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Identification of Prolactin-Like Proteins Synthesized by Normal Murine Lymphocytes

Cited by 78 publications

References 4 publications

Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation.

Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation.

Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor.

Prolactin increases CD4/CD8 cell ratio in thymus-grafted congenitally athymic nude mice.

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